The long-term goal of this research is to establish a robust and accurate MRI method for estimating absolute cerebral blood volume (CBV) and to use this technique for clinical studies of brain diseases, such as acute stroke and Alzheimer's Disease. For this project, the specific aims are: 1) To develop the pulse sequence and related algorithms that allow quantification of absolute CBV using pre- and post-contrast MR images; 2) To evaluate the effects of other confounding factors, to optimize the imaging protocol, and to validate the MRI results using PET CBV measurements. CBV, defined as ml of blood per 100 ml of brain tissue, is an important physiological marker in many neurovascular diseases. Furthermore, it is of critical value in the diagnosis and/or monitoring of treatment for many other brain diseases that are non-vascular in origin. Existing techniques for the measurement of CBV either suffer from limited spatial resolution (e.g. PET) or require additional knowledge about the arterial input function (e.g. dynamic susceptibility contrast MRI). In this project, a novel approach will be developed for the accurate measurement of absolute CBV using Vascular-Space-Occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T1 shortening effect of the contrast agent Gd-DTPA. Two VASO images are acquired before and after contrast agent injection, resulting in a difference image that can be used to determine CBV. The key novelty of the proposed approach is that the estimation of CBV does not require knowledge or assumptions about vascular morphology. This is expected to provide a more accurate estimation of CBV compared with existing methods. The imaging protocol will be optimized by investigating various confounding factors that may cause error in the CBV estimation, including contrast agent concentration, MR receiver coil sensitivity profile, transverse relaxation effect of the contrast agent, effect of water exchange in the capillary bed, and effect of leakage in the blood-brain-barrier. The MRI CBV results will be validated using PET CBV measurements. Relevance: Many diseases in the brain are related to the blood supply to the brain. Therefore, it is of substantial value for physicians to have knowledge about the amout of blood present in the brain, often referred to as cerebral blood volume (CBV). In this project, a new technique will be developed to measure CBV in human brain using MRI. [unreadable] [unreadable] [unreadable]